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RNA binding protein KSRP mediated miRNAs processing reciprocally regulates granulocytic and monocytic differentiation

ABSTRACT: KSRP is involved in RNA processing at multiple levels including alternative splicing, mRNA stability, mRNA localization and translation efficiency. Dysregulation KSRP can cause to hematological malignancies. However, the direct contribution of KSRP to myeloid lineage differentiation is poorly understood. KSRP, as a KH-type splicing regulatory protein, which interacts with single-stand AU-rich element containing mRNA and mediated mRNA decay, also serves as a component of Drosha and Dicer complexes and regulates the biogenesis of miRNAs. Whether KSRP mediated miRNAs maturation participated in myeloid lineage differentiation is unknown. Here, we analysis the miRNAs processing during over-expression KSRP in THP-1 cells by poly-A(riched) RNA-seq and miRNA-Seq. Our results suggest that KSRP regulate a class of miRNAs maturation and have a critical function in myeloid lineage differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87318 | GEO | 2017/08/01

SECONDARY ACCESSION(S): PRJNA344330

REPOSITORIES: GEO

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KSRP-mediated Transcriptome reshaping

Project description:KSRP knock-down and BMP2 treatment produce a largely overlapping reshape of the transcriptome in C2C12 cells. microRNAs (miRNAs) are essential regulators of development, physiology, and evolution with miRNA biogenesis being strictly controlled at multiple levels. Regulatory proteins, such as KH-type splicing regulatory protein (KSRP), modulate rates and timing of the enzymatic reactions responsible for maturation of select miRNAs from their primary transcripts in response to specific stimuli. Induction of myogenic miRNAs (myomiRs) is essential for muscle differentiation with KSRP phosphorylation being required to convey myogenic signals to enhanced myomiR maturation. Here we show that either KSRP silencing or Bone Morphogenetic Protein (BMP)2-signaling activation in mesenchimal C2C12 cells prevented myogenic differentiation while induced osteoblastic differentiation as revealed by the reshaping of the whole transcriptome analyzed by RNA deep-sequencing. The most striking feature common to both BMP2 signaling activation and KSRP silencing was a blockade of myomiR maturation. Our results demonstrate that phosphorylated SMAD proteins, the transducers of BMP signaling, associate with KSRP and block its interaction with primary-myomiRs. This, in turn, abrogates KSRP-dependent myomiR maturation with the knock-down of SMAD4, 5, and 9 being able to rescue KSRP function. SMAD-induced blockade of KSRP-dependent myomiR maturation, in parallel to the well known SMAD function on gene transcription, inhibits C2C12 cell differentiation into myofibers and contributes to orient cells towards osteoblast lineage. We propose that remodeling of co-regulatory complexes affecting primary-miRNA processing is a mechanism well suited to guide cell fate determination in eukaryotes. Total RNA was prepared from 1. untreated mock-transfected C2C12 cells; 2. BMP2-treated mock-transfected C2C12 cells; 3. untreated shKSRP-transfected C2C12 cells and analyzed by RNA-seq

2013-06-25 | E-GEOD-38907 | biostudies-arrayexpress

KSRP-mediated Transcriptome reshaping

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KSRP deficiency attenuates the course of pulmonary aspergil-losis, associated with elevated pathogen-killing activity of in-nate myeloid immune cells

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Expression data from KSRP overexpression and knockdown lung cancer cell

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2016-06-16 | E-GEOD-83388 | biostudies-arrayexpress

Expression data from KSRP knockdown lung cancer cell

Project description:KSRP depleted CL1-0 cells were used to identify genes regulated by KSRP We used microarrays to detail the global programme of gene expression underlying metastasis and identified distinct classes of KSRP-regulated genes during this process.

2017-07-26 | GSE101842 | GEO

Expression data from KSRP overexpression and knockdown lung cancer cell

2016-06-16 | GSE83388 | GEO

Destabilization of Nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fiber formation

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2014-04-26 | E-GEOD-57113 | biostudies-arrayexpress

Destabilization of Nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fiber formation

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High-throughput mRNA-sequence of KSRP knock down mouse primary hepatocytes

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